OBJECTIVE To ascertain the antibiotic resistance patterns and plasmids of Staphyl coccus aureus and coagulae negative staphylococci isolated from different clinical specimens in Lagos, Nigeria. METHODS Prospective study involving the screening of specimens of blood, urine, skin and soft tissue infections, vagina, urethra, eye, ear, nose, pleural fluid and seminal fluid obtained from patients attending the Lagos University Teaching Hospital (LUTH) and Providence Hospital Diagnostic Laboratories, Lagos, Nigeria. METHODS A laboratory based study conducted in the Microbiology Unit, University of Lagos and the National Institute for Medical Research (NIMR) Lagos, Nigeria. The patients were from different communities in Lagos. METHODS A total of 200 patients that were positive for the presence of S. aureus and coagulase negative staphylococci (CONS) were employed in the study. METHODS Frequency of isolation of S. aureus and coagulase negative staphylococci (CONS) from the different clinical specimens determination of their resistance profile using standard techniques for the isolation of both organisms and the Kirby-Bauer disc diffusion method for antibiotic testing. RESULTS All the S. aureus and CONS isolates were sensitive to novobiocin and ofloxacin. Ninety eight (80 pc) of S. aureus isolates were resistant to tetracycline (Tet), 73 (60 pc) to Streptomycin (Str), and 49 (40 pc) to Chloramphenicol (Chl). All the S. aureus isolates were resistant to Penicillin (P) and only two (2 pc) and four (three pc) were resistant to Cefuroxime (Cxm) and Ceftriasone (Cro) in that order. Twenty six (21 pc) of S. aureus isolates were resistant to Methicillin. For CONS, 92 pc were resistant to Penicillin, 47 (60 pc) to streptomycin and 40 (51 pc) to tetracycline. Nineteen (24 pc) were resistant to Methicillin. Further antibiotic sensitivity results revealed the following patterns: 87 (71 pc) and 29 (36 pc) of S. aureus and CONS respectively showed P RTet"R, pattern of resistance. The resistance pattern PREryRGmRCazRCxmR was shown by only one (17 pc) of S. aureus and none (Opc) of CONS. Only 59% and four pc of S. aureus and CONS isolates showed resistance pattern ChlREryR, CazR respectively. Results of plasmid profiles showed that 48 (96 pc) of 50 S. aureus and 26 (87 pc) of 30 CONS isolates harboured one or more plasmids of molecular sizes ranging from 1.0 Kb to 19.5 Kb. Nine (19 pc) of 48 S. aureus and three (12 pc) of CONS isolates showed plasmid identity. CONCLUSIONS We assert that although isolates of S. aureus and CONS showed multiple antibiotic resistance which could be plasmid mediated, only about five pc of both organisms showed resistance pattern ChlREryRCazRTetRCxmRSxtRGmR and EryRGmRCazRCxmR and this is of chemotherapeutic importance. Both organisms, were highly sensitive to Ceftriazone, Ceforoxime and Gentamicin. The high levels of resistance of many antibiotics may be attributable to indiscriminate use or antibiotic abuse in the community.